The efficient delivery of nucleic acids to targeted cells and tissues, as well as the subsequent transfection of such nucleic acids into such targeted cells and tissues remains a technical challenge. For example, as a result of the size and charge of nucleic acids such as DNA and RNA, the ability to effectively and efficiently deliver such nucleic acids to and/or to transfect such targeted cells and tissues is often limited.
One approach to improve the delivery of nucleic acids and polynucleotides to target cells and tissues has been the liposomal encapsulation of nucleic acid in lipids, and in particular cationic lipids. The electrostatic interaction of the cationic lipid with nucleic acids facilitates the formation of lipid-encapsulated nucleic acid particles in size ranges which may be suitable for in vivo administration. The positively charged cationic lipid on the outer particle surfaces facilitates the interaction of the cationic lipid-based liposome with the negatively-charged cellular membranes, thereby promoting fusion of the liposome with the cellular membrane and delivering the liposome and/or emptying the nucleic acid contents of the liposome intracellularly. Although several advantages of using liposomes to facilitate the delivery of therapeutic agents to target cells and tissues have been previously described, many problems still exist in in vivo, ex vivo and in vitro applications. For example, many of the cationic lipids are generally toxic to the targeted cells, and accordingly may be of limited use. Furthermore, liposomal carriers may not be the most efficient means of delivering nucleic acids to target cells or to subsequently transfect such cells.
Novel approaches and therapies are still needed to enhance the delivery and/or transfection efficiencies of polynucleotides and nucleic acids, particularly those delivered in liposome delivery vehicles, such as encapsulated liposomal formulations. The development of new and improved liposome delivery vehicles and liposomal formulations that demonstrate enhanced delivery and/or transfection efficiencies would further advance nucleic acid based therapies for the treatment of diseases, such as gene and mRNA silencing therapies, that may benefit from gene replacement therapies, mRNA delivery therapies, and/or other therapies that include the intracellular delivery of nucleic acids for the modulation of gene, protein and/or enzyme expression.